If you haven’t already heard, intermittent fasting has been gaining popularity when it comes to weight-loss lately, and there are several reasons why. There have been countless weight-loss programs introduced to America, but there is something different about this particular strategy that sets them apart. What is intermittent fasting? Intermittent fasting is a weight-loss strategy that involves regular short-term fasts to help regulate weight and appetite with calorie counting not necessarily required.

Intermittent Fasting Methods

1. 16/8

In this method, you will skip breakfast every day and schedule meals within an 8-hour window, such as from 12-8pm. The “16/8” stands for 16 hours fasting (refraining from eating or drinking anything but water) and 8 hour window for meals.

2. Eat-Stop-Eat

This fasting method requires a 24-hour (full-day) fasting one-two times a week.

3. 5:2 Diet

This diet includes two days a week of consuming only 500-600 calories within those days, while eating normally the other 5.

Following any of the three methods listed above should be effective as long as you don’t overeat on the non-fasting periods. Although calorie counting is not necessary, intermittent fasting also practices portion control. Overall, these methods should result in reduced caloric intake as well as help you begin to shed excess weight.

Intermittent Fasting and Hormones

The body stores energy using calories (body fat). When we don’t eat, the body will alter ways to be able to access the stored energy. The body will make changes in several important hormones as well as activity in our nervous system when we fast. Certain changes in your metabolism during the fasting periods include:

- Human Growth Hormone: These levels may shoot up to 5 times as high during a fasting phase. The human growth hormone is responsible in helping with fat loss while building muscle mass and other benefits.

- Norepinephrine (noradrenaline): During fasting, the nervous system will send norepinephrine to our fat cells to aid in breaking down body fat that are able to be burned to create energy.

Overall, fasting short-term can create several changes in our body to make fat burning easier to do including reducing insulin levels and increasing fat-burning and increasing muscle mass for those who train and exercise.

Intermittent Fasting - Consume Less Calories and Lose Weight

Besides the fasting aspect, you will also naturally consume less calories with this method. Again, it is important to note that effectiveness coincides with making sure you don’t binge or overeat on eating periods or non-fasting days. Some people may consider this time to have “cheat” meals or cheat days, but it should be considered another normal meal. Following this will result in a decline of your daily calorie intake.

When Can I Expect to See Results with Intermittent Fasting?

On average, following an intermittent fasting strategy for a period of 3 weeks can reduce your body weight by 3-8%! Some people will lose a little over half a pound a week using intermittent fasting, and over double (1.65 pounds a week) utilizing the alternate-day fasting method (Eat-Stop-Eat). With these impressive data, there is no question intermittent fasting is a great method to give a shot.

Intermittent fasting benefits don’t stop at just weight loss either. You can expect improvements in your metabolism, expanded lifespan, quality of life, as well as help prevent from certain chronic diseases as well.

How to Maximize Effectiveness with Intermittent Fasting

Take into consideration the below to maximize in weight loss using intermittent fasting:

1. Quality of Food - Treat your body like a temple! What are you putting in it? Stick to eating primarily simple foods with few ingredients and whole foods. Try to avoid processed foods and products with GMO.

2. Calories - You don’t have to count your calories, but gauge it. Try to eat a regular portioned meal during non-fasting periods so you don’t sabotage your progress on the fasting days.

3. Consistency - Like any other weight loss strategy, consistency is key to making weight-loss effective. Do not deviate from the intermittent fasting method you chose and over time, you will start to see the results you’re looking for, but don’t forget #4 - patience.

4. Patience - Working any changes into your daily life will take some for your body to adapt to. Be consistent with your intermittent fasting schedule and be patient to see results.

Although there are several types of weight loss methods to follow, intermittent fasting is a simple one that allows the body to alter itself to increase fat-burning and muscle gain. Intermittent fasting may be the reliable tool you’ve been looking for to lose weight. Along with weight loss, it has many other advantages such as preventing disease, boosting your metabolism, and benefits critical hormones. Fasting is not for everyone, but it works for a lot of people. Give it a shot, and see whether or not intermittent fasting works for you! Ageless Forever also offers personalized weight loss programs to suit your unique needs. Whatever you choose, make sure you are putting your health first to help you stay Ageless.

With summer just around the corner, it is time to get serious about our diets and workout regimens to get our bodies ready to bare some skin. As many of you know, diet is just as important (if not more important) as exercise. The goal for your diet is to significantly reduce your appetite to prevent junk food impulses, lose weight quickly, and improve your metabolism. Maintaining a proper diet will keep you fuller and more satisfied throughout the day.

If you are looking to shed some pounds and not sure how, keep reading. We’ve assembled a list of 5 foods to include in your grocery list that will help you reach your goal weight along with some helpful tips and recommendations to consider.

5 Best Foods to Help You Lose the Weight

1. Shrimp

This tasty seafood is not only high in protein but low in calories and carbohydrates as well. It is easy to prepare, easy to incorporate into many dishes and can actually lower your appetite by increasing CCK, a hormone in your stomach that prevents hunger.

2. Whole eggs

Contrary to its myth, eggs are high in cholesterol, but does not affect our blood cholesterol and are among one of the best foods for you to consume for weight loss. Eggs are incredibly nutrient-dense (especially the yolk), high in protein, high in healthy fats, while being low in calories which leaves you feeling satiated and satisfied even on a restricted diet.

3. Avocado

Fruits tend to be high in carbs, but avocado is unique. Avocados are loaded with healthy fats, particularly high in the same type of fat found in olive oil (monounsaturated oleic acid). Avocados also contain lots of water, so they aren’t as energy-dense. Adding some of this fatty fruit into your salad can actually help boost your nutrient intake from the vegetables. Foods with healthy fats are great to keep you feeling satisfied longer, a key tool for losing weight.

4. Chia Seeds

Don’t let their tiny size fool you, they are considered one of the most nutritious foods on the planet. Chia seeds are a little high on the carbohydrates side (containing 12g per oz), but about 92% of that is fiber. Due to their high-fiber content, chia seeds can absorb up to 11-12 times their weight in water and expand in your stomach and help curb your appetite, preventing overeating. Keep in mind these seeds are a little high in fat as well (4.5g per tablespoon). Just incorporate chia seeds in moderation, that way you won’t exceed your daily calorie limit.

5. Coconut Oil

Coconut oil contains healthy fatty acids that help you feel full while boosting metabolism. Studies show that adding coconut oil to your diet can help eliminate fat, especially the bad fats in the abdominal area. Coconut oil is thermogenic, which means it tends to increase fat burning energy. Cooking with this instead of some other oils will be a great alternative to aid your weight loss journey.

Weight Loss Tips

1. Enroll in Weight Loss Programs

At Ageless Forever, Dr. Pierce and his medical team specializing in diet and nutrition offer personalized weight loss programs based on your specific needs to not only lose the weight, but to keep it off. Our programs focus on 2 phases - the weight loss phase, and the maintenance phase, utilizing strategies tailored to individual clients. These weight loss programs help provide more monitoring and direction for clients who prefer more guidance to ensure better chances of a successful weight loss journey. Commitment to our program at Ageless is a great way to hold yourself accountable to stay on track with a proper diet.

2. Less Sugar & Starches

Cutting back on sugars and starches (carbohydrates) will help you cut weight significantly. Simply consuming less sugars and starches will help control your hunger levels and result in cutting back a lot of calories. As your body adjusts, it will begin to feed off of stored fat for energy instead of carbs. Less carb consumption also lowers your insulin levels, causing your kidneys to rid the body of excess sodium and water. This helps reduce unnecessary bloating and water weight. Many people who committed to this rule have reported shedding up to 10 pounds in body fat and water weight within the first week without feeling deprived of food.

3. More Protein, Fat, & Vegetables

Include a protein, fat, and low carb vegetable source with every meal. Planning your meals in this way will help maintain your daily recommended carb intake (20-50g). Don’t be afraid of protein! The importance of consuming plenty of protein cannot be expressed enough. A high-protein diet has been shown to boost metabolism by burning an extra 80-100 calories a day! Protein actually helps reduce cravings and the desire for late-night binging by half while keeping you feeling full and satisfied so you actually consume less calories a day. Get rid of the misconception that consuming fats will make you gain fat! It is simply not true. Healthy fats will also keep you feeling satisfied longer after every meal to prevent unnecessary snacking. Load up your meals with plenty of low-carb vegetables without fear of going over the 20-50 net carbs per day recommendation. A diet filled with protein, healthy fats, and low-carb vegetables ensures ample fiber, vitamins and minerals required to maintain a healthy diet.

4. Lift Weights

Exercise is not required, but of course recommended to lose weight. Working out a consistent 3-4 times a week is a great way to establish an active lifestyle. If you are new to exercise at a gym, ask a trainer for advice. Lifting weights will help you burn plenty of calories while continuing to stimulate your metabolism. Studies show that low-carb diets will help you gain some muscle while shedding the excess body fat. Cardio exercise such as walking, jogging, swimming, and cycling are also great alternatives for those who are unable to lift weights for health reasons.

5. CoolSculpting

Do you still have problem areas with stubborn excess fat no matter how hard you try with good diet and exercise? You may want to consider learning more about CoolSculpting. There’s a reason why CoolSculpting is the world’s #1 non-invasive fat removal treatment. This treatment freezes and eliminates unwanted fat cells without use of needles, surgery, or recovery. Over 4 million patients have been treated with CoolSculpting and have had remarkable results. Do some more research to see if this treatment is right for you.

Now that you’ve got a good foundation to get going, there is no reason to put off your health any longer. It is never too late to improve an unhealthy lifestyle. Fuel your body with the right foods including high protein, low-carbs, and healthy fats while adding some weight-lifting exercise into your week consistently and you will see the results. Not only will you start to look better as the pounds begin to melt off, you will feel a lot better in terms of your mood, energy levels, and self-confidence. Make this change for yourself, you deserve it. Good luck on your journey to a healthier you! Cheers.

As we grow older, we can expect our bodies to go through some significant changes that start from within that will eventually start to show physically. It’s alright, folks...It’s all a natural part of life. What can be done? How can we retain that youthful look? Unfortunately, the fountain of youth is still yet to be discovered, but there are certain things you can do assist you to continue to look and feel young and vibrant including what we put in our diets. Many people dream of reviving & retaining their youthful, radiant skin and although there is no magic pill to immediately transform you, there are things you can eat to bring you closer to your goal. In fact, studies have shown certain foods can slow down our aging process or even reverse effects. We have gathered a list of some great anti-aging foods to put on your grocery list and a few may surprise you! Keep reading to find out more.

Oats. Not only are they packed with antioxidants, oats are rich in soluble fiber and helps rid the body of “bad” cholesterol. Oats are complex carbohydrates that give you a natural boost of energy throughout the day, lowers cholesterol levels and are low-glycemic. What can low-glycemic mean for you? Low-glycemic foods help prevent aging hormones from developing. Oats will help defend against skin cell damage and relieve skin irritation. You can even find facial masks using oatmeal as one of their key ingredients, so make sure to keep this goodie stocked in your pantry.

Oranges.One of the most well-known benefits oranges provide is Vitamin C, which then encourages more production of collagen to help keep our skin supple and firm. As we age, our bodies naturally produce less collagen and that’s when you’ll start to see signs of wrinkles and sagging skin. Oranges will help produce more collagen and reorganization of new collagen fibers in your skin. Oranges will supply you energy, fiber, loaded with water, and your immune system will thank you! Oranges will help you feel good, help hydrate your skin and cells, and is considered a great snack to get you through the day.

Dark Chocolate. Raw cacao, the main ingredient found in chocolate contains an abundance of over 300 antioxidants, aiding in slowing down aging and improving your immune system by protecting your body against viral and bacterial infections. Do you ever find that chocolate makes you feel a little better on a rough day? It’s not just the comforting yet intoxicating taste of chocolate that’s improving your mood. Cacao is actually considered an organic antidepressant to relieve anxiety, depression, and promotes feelings of happiness.

Black Sesame Seeds. These seeds are loaded with iron and vitamin b which helps prevent and reverse signs of aging. Black sesame seeds also contain calcium and magnesium to stabilize blood pressure and help build strong bones. You can also find copper and zinc to sharpen your immune system, reduce pain and swelling for arthritis and other inflammatory conditions, and helps provide a solid foundation for supple bones, skin, and joints.

Green Tea. People in Japan have been known to have the longest lifespans in the world, and hold the top spot as the largest consumer of green tea. Purely coincidental? Think again...Green tea offers a variety of anti-aging benefits such as slowing down the aging process due to its high antioxidant content. Green tea is also rich in flavonoids, known to contribute to healthy knees, and reducing damage to your arthritis joints that happens as you age.

Salmon. Fish is a great way to integrate protein and healthy omega-3 fats in your diet, and salmon is a great source for both with low mercury content. Some studies even suggest omega-3s can prevent skin cancer cells from growing. Protein is a great aid in repairing and stimulates growth for your muscle cells.

Raw Honey. Ahh yes, nature’s sugar. The pure, unfiltered, unpasteurized sweetener made from bees contain multiple benefits for your skin and body. Raw honey acts as a natural cleanser, is an amazing hydrator for the skin to smooth out wrinkles, lightens dark circles and fights specific bacteria known to cause pimples and acne. It is very common to find face mask recipes that utilize honey as a core ingredient. Try to get your hands on the raw honey and avoid the processed kind. Honey that has been processed gets filtered and stripped of a lot of the good antioxidant stuff that is beneficial.

Notice a similar recurring theme here? Yes, the more antioxidants in the food, the better it is to help to fight against aging! Don’t limit yourself to just the few superfoods we’ve mentioned above either. There are plenty of other great foods available to achieve what you are looking for. It’s simple. Just make sure you keep your diet packed with nutrients such as antioxidants, omega-3s, vitamins, copper, protein foods to continue to help your skin and body feeling and looking youthful. If you want reassurance that you get enough of the antioxidants and botanicals your body needs, look into our UltraNutrient® supplements crucial for cardiovascular, immune, & cellular health. Although we can’t freeze time or avoid aging, it is important we do what we can to take care of our bodies which will also help naturally slow down the aging too. It’s a win, win! Let’s work with what we’ve got and take charge of our health. You don’t have to do it alone...We are right here with you.

If you are following the anti-aging news, you’ve heard about the supposed benefits of chronic calorie restriction for increasing longevity. These claims are based on research done in various species such as flies, worms and mice.

Here I will explain that chronic calorie restriction makes it impossible to implement and reap the health benefits of an active lifestyle with regular exercise, and causes severe health consequences for humans.

While animal studies can and do shed light on what’s going on at mechanistic level, we have to be very careful and resist the temptation to extrapolate results from animal experiments to humans.

Here I will make the case that chronic calorie restriction actually counteracts the prospects of a healthy vital long life.

Background

While the news on the anti-aging effects of calorie restriction are relatively recent in popular media, calorie restriction has been studied scientifically in different species (worms, spiders, rodents, dogs, cows and monkeys) since the 1930s.[1, 2] Results of most studies demonstrated that substantial reductions of food intake to 30-60% below spontaneous intake levels decreases the incidence and age of onset of many age-related diseases, and increases both average and maximum lifespan.[3, 4]

How does it work?

The exact mechanisms by which calorie restriction slows down the aging process, prevents development of aging-related diseases and extends of average and/or maximum lifespan, are currently under intense scientific scrutiny. Calorie restriction causes significant alterations in energy metabolism, oxidative damage, insulin sensitivity, and functional changes in both the neuroendocrine and sympathetic nervous systems.[5] On a molecular level, some identified mechanisms underlying the pro-longevity effects of calorie restriction include the following:

However, these molecular level effects have mainly been demonstrated in laboratory animals. Calorie restriction in humans has many other effects (some of which have no equivalent in animals) that are not conductive to health (more on this later). Thus, we have to look at all the joint effects of caloric restriction, separately for each species, before we can draw conclusions about its final outcome for that particular species.

Calorie restriction – just another fancy name for dieting?

Calorie restriction will obviously benefit anybody who is carrying around excess body fat. Nothing new here; go on a diet (restrict your caloric intake and exercise), lose the flab, reduce your risk factors (such as insulin resistance, high blood pressure, triglycerides (blood fat) etc.) and you will live longer. So don’t let advocates of calorie restriction fool you when they support their arguments by referring to studies on overweight (e.g. “overfat”) and obese subjects [19-22]. Here I am focusing on the effects of calorie restriction in non-obese folks.

Drum roll… does chronic calorie restriction work in non-obese humans?

This is a controversial question even among researchers who are actively studying calorie restriction. The opinions as split; roughly half of them taking the position that yes, calorie restriction can be applicable and confer health benefits to humans, while the other half argue that calorie restriction isn’t applicable to non-obese humans and instead poses a risk for detrimental health effects [23] (more on this later).

Why wouldn’t calorie restriction have the same beneficial anti-aging effects in non-obese humans as in non-obese animals?

Humans differ in many ways from rodents and non-human primates. First, laboratory animals live in artificial environments and often are “metabolically morbid”.[24, 25] It is noteworthy that calorie restriction increases life span most in rodents that have a large spontaneous food intake, but has a minor effect on lean litter mates.[26]

Second, rodents and non-human primates (even rhesus monkeys) have much shorter life spans than humans, and have been selected under very different evolutionary pressures.[27-30] This will cause them to respond differently to food restriction and other environmental situations.[23, 29] This is especially true when it comes to aging, because aging is not a programmed process in the sense that no genes have evolved specifically to cause damage and aging.[31] Prominent gerontologists all agree that aging is a result of evolutionary neglect, not evolutionary intent.[32-35] Mechanisms of aging might therefore not be expected to be as highly conserved between distantly related organisms as are mechanisms of development and metabolism.[31]

Third, in comparison to humans, exercise appears to have only minor benefits in terms of lifespan in rodents.[36-39] But even so, exercise does improve average lifespan of rats independent of calorie restriction [40], and increases in food intake is not harmful when balanced by an increase in exercise induced energy expenditure.[40]

We all know about the health promoting and anti-aging effects of exercise (see below) and that the majority of us don’t exercise enough. An important consequence of calorie restriction in humans is a reduced spontaneous physical activity level.[41-44] Because rodents are not troubled by heart disease as humans, they don’t derive as much benefit as we do from elevated exercise [38]. And they are less negatively affected by reduced exercise and physical inactivity.[38] For us humans, a reduced physical activity level will have major detrimental health effects that most likely would offset any - if possible - benefits of caloric restriction.

Calorie restriction is not the only example of animal experimental results that don't directly apply to humans. Other examples are CLA [45], leptin [46, 47] and torcetrapib [48, 49] (a drug use to elevate HDL “good cholesterol” levels). These all showed a lot of promise in rodents but failed to replicate their beneficial effects in humans, and torcetrapib and CLA actually ended up causing more harm than good in humans.[45, 48, 49] Another prime example that results from animal experiments cannot be extrapolated to humans is growth hormone (GH) and IGF-1. In animals, GH/IGF-1 deficiency confers longevity [50, 51]. However, in humans, GH/ IGF-1 deficiency is a risk factor for cardiovascular disease and early death (I will cover this in much more depth in an upcoming article).[52]

Adverse health effects of chronic calorie restriction in humans

Chronic calorie restriction in non-obese people results in the following detrimental effects:

By reducing spontaneous physical activity and energy expenditure, calorie restriction lowers energy flux. Energy flux refers to the absolute level of energy intake and expenditure under conditions of energy balance (that is, when caloric intake equals caloric output).[66, 67] A high energy flux is a key mechanism contributing to the elevated resting metabolic rate seen in habitually exercising people [68], which contributes to protection against obesity.[69] For example, a low resting metabolic rate (RMR), expressed in relation to fat-free mass, is a risk factor for subsequent fat gain.[70] After 4 years of follow-up, the risk of gaining 10 kg was approximately 7 times greater in those subjects with the lowest relative RMR than in those with the highest RMR. The subjects who gained more than 10 kg had a relative RMR that was only 70 calories lower per day (24 hour period) than those who didn't gain. The total daily (24-hour) energy expenditure was estimated to be responsible for up to 40% of the weight change.[70] This points to the importance of RMR in obesity prevention, in addition to total energy expenditure. Further support for the importance of keeping a high energy flux comes from a study showing that the age-related decline in RMR is related to age-associated reductions in exercise volume and energy intake, and does not occur in those who maintain exercise volume and/or energy intake at a level similar to that of younger peers.[71] A high energy flux also increases RMR in younger adults [66], and is therefore has benefits regardless of age.

A notable finding that totally counters the proposed benefits of calorie restriction is that a high physical activity energy expenditure - which is reduced by caloric restriction [41-44, 55, 56] - is strongly associated with a lower risk of mortality [72], less deaths and preserved health [73] (more in this below).

The cortisol elevation seen with calorie restriction has dual negative effects in that it not only adds a bite to your appetite [74] and thereby makes calorie restriction hard to maintain for longer periods of time, but also breaks down muscle tissue.[75] It's notable that a reduced physical activity level, which as mentioned above is a consequence of calorie restriction, amplifies the catabolic effect of cortisol on muscle.[75] Thus, long-term calorie restriction not only elevates cortisol, but also contributes to making muscles more susceptible to its catabolic effects. The muscle catabolic effect seen with calorie restriction will further exacerbate sarcopenia (age related muscle loss) and its consequences [76-81], which plagues humans but not worms, fruit flies and mice.

Considering these side-effects, it is not surprising that there is no evidence showing that calorie restriction life span in lean humans.[19, 82] And there probably never will be. Thus, it is ironic that the (CR) society's goal is to "help people of all ages live longer and healthier lives by eating fewer calories with adequate nutrition)".

I want to comment on the CR society statement of adequate nutrition. There are two important issues here:

First, adequate nutrition, defined as "covering survival needs" is not optimal nutrition. It is well known that several nutrients (e.g. omega-3 fats, protein, vitamin D, vitamin K2, calcium, vitamin E, vitamin C, choline etc.) have major health promoting effects when ingested in larger amounts than necessary to cover just survival needs. Second, adequate nutrition cannot make up for the serious side effects of calorie restriction listed above.

The negative psychological and social consequences induced by chronic calorie restriction in humans have no equivalent in animals. I want to point out that even researchers who are advocates of calorie restriction have expressed their concern and concluded that chronic calorie restriction would be harmful in lean people [19].

What about the Okinawans?

The Okinawan population is renowned for their reduced morbidity and mortality having the greatest percentage of centenarians anywhere in the world.[83, 84] Compared to Americans, the mortality rate of Okinawans between the age of 60 and 64 years is half that of the American population. The death rates due to heart disease, stroke, and cancer is approximately 30–40% lower compared to the rest of Japan and even more so compared to the United States. Why do Okinawans have the longest disability-free life expectancy in the world?

Calorie restriction proponents believe the answer is their diet. The Okinawans consume a diet lower in calories compared to the rest of Japan by 20%, and the United States by 40%. Their diet mimics the amount of caloric restriction imposed on experimental animals, and appears to also mimic the effects of the calorie restricted diet in animals. However, the Okinawan diet provides more than just "adequate nutrition". It consists mainly of vegetables, legumes, fruits, seaweed, fish, and unique vegetable varieties (eg konnyaku, shiitake Mushroom, hechima, gobo, tofu) and herbs/spices (Ucchin, Fuchiba, Hihatsu, Ichoba), which are well-known for the health promoting effects.[85-87] In contrast to the Western diet, the Okinawan longevity foods are highly anti-inflammatory and anti-acidogenic [87]. The Okinawans also have a very different stress-free ancestral lifestyle and culture that the Western world.[88] Thus, attributing their healthiness and longevity to their calorie restriction is a major flaw. Another fact to bear in mind when calorie restriction proponents bring up the Okinawans as evidence for their position is that none of the Okinawans have achieved the maximum life-span recorded by the French woman Jeanne Calment (122 years).

Living Fast, Dying When?

More than 100 years ago it was documented that energy expenditure expressed in relation to body size and lifespan was relatively fixed.[89] This led to the conclusion that energy used up faster will shorten lifespan, and the rate of living theory of aging. Based on this theory, things wear out with use and the faster they are used, the sooner they wear out. In line with this reasoning, the reduced energy expenditure seen with calorie restriction has been proposed to be one mechanism behind its longevity extending effects in different organism and animals.[90]

However, this has been refuted by inconsistencies among birds and bats which live several fold longer than do mammals of comparable body size and resting metabolic rate.[91] Additionally, rats exposed to long duration cold exposure increased their energy expenditure, but did not have a shortened lifespan.[92] These studies and others [93, 94], together with falsification of the original assumptions that gave rise to the rate of living theory [95], have completely refuted the concept that an increased energy expenditure decreases longevity. Further support comes from a study showing that retardation of the aging process can occur without the restriction of calories or any other nutrient per unit of lean body mass.[93]

Energy expenditure data in humans also boldly refute the rate of living theory of aging. An increase in free-living activity energy expenditure of approx. 300 calories/day has been associated with a 32% reduced risk of mortality among elderly, even after adjusting for age, gender, race, weight, height, percent body fat, sleep duration, health status, education, prevalent health conditions, and smoking behavior [72]. This was confirmed in a follow-up study which reported that activity energy expenditure is strongly associated with reduced mobility impairment and preserved physical function.[96] A growing body of evidence confirms that activity energy expenditure might be an important determinant of lifespan in humans.[97, 98] Regular exercise that improving fitness and increases muscle mass is a well documented anti-aging strategy [98], and fitness and muscle growth can only be achieved via an increased energy flux. Thus, the importance for physical activity for human health and longevity is a major counter argument against calorie restriction in humans. This is supported by data showing that exercise may promote longevity through pathways common to effects of caloric restriction.[99] This further reduces the potential of caloric restriction as a viable strategy for humans.

Does calorie restriction work by reducing intra-abdominal “belly” fat?

A research group at the Institute for Aging Research, Albert Einstein College of Medicine have hypothesized that the ability of calorie restriction to improve longevity is by reducing visceral fat, i.e. intra-abdominal “belly” fat.[100] Surgical removal of visceral fat, but not subcutaneous fat removal, closely resembles the effects of prolonged calorie restriction. [101] This suggests that decreased visceral fat could largely account for the beneficial effects of a reduction in food intake. Additionally, earlier studies have a shown a causal role for visceral fat in age-related metabolic decline, impaired glucose metabolism (similar to rodents), and for the development of cancer (similar to rodents) and atherosclerotic vascular disease (in humans).[72]

This is good news, as exercise dose-dependently reduces visceral fat in humans [102, 103] and results in fat loss with a smaller degree of calorie restriction.[104] And importantly, exercise also improves aerobic fitness, which has other important cardiovascular and metabolic implications that cannot be achieved by calorie restriction alone.

What about calorie restriction mimetics?

While evidence is accumulating that long-term calorie restriction in non-obese humans falls short of the expectations as the ‘‘fountain of youth’’ as seen in lower organisms and animals, research has identified substances – called calorie restriction mimetics - that activate some the same molecular and signaling pathways as calorie restriction does.[105, 106]

These so called calorie restriction mimetics have potential to confer health benefits without imposing calorie restriction and risking its side effects, and is an emerging research field.[107-112] The focus of calorie restriction mimetic research is to discover and activate nutrient sensors, to achieve at least some of the anti-aging and life-extending effects of calorie restriction that have been seen in animals.[113]. Some examples are the polyphenols resveratrol and EGCG (epigallocatechin-3-gallate), and the drug metformin (which I will cover separately in an upcoming article).[105, 106]

However, although currently researched calorie restriction mimetics appear to confer life and healthspan extending impacts across numerous cell types and model organisms via for example SIRT1/AMPK interaction, the downstream impact on genome function (gene expression) is varied across cell-type, organism-type, and compound-type, in addition to variations in experimental details (such as exposure times, drug concentrations).[106] This suggests that although mechanisms mediating health and lifespan in response to calorie restriction and calorie restriction mimetics are similar, the effects on gene expression (which is of paramount importance for human longevity) mean that these compounds may not be direct mimetics of calorie restriction across the board.

Exercise as a “human calorie restriction strategy”

Considering the downsides of chronic calorie restriction for humans, and the vast amount of research proving the health promoting effects of regular exercise in humans, including increased longevity and vitality [114-117], one may wonder if exercise could be a “human calorie restriction strategy”?

Even though exercise and caloric restriction affect energy metabolism in a diametrically opposite manner, many of the effects of calorie restriction that have been seen in animal experiments are the same as those that occur in humans in response to exercise, such as improved mitochondrial function, oxidative metabolism, autophagy, ROS detoxification, genomic stability, see figure 1.[112] This can explain the similar health benefits of calorie restriction in animals and exercise in humans. However, as indicated in figure 1, while calorie restriction only causes weight loss, exercise not only improves body composition (by reducing body fat and increasing muscle mass) but also improves muscle and cardiovascular function.

Figure 1. Common and distinct effects of exercise and caloric restriction.[112]

Figure 1 also shows the benefits to humans conferred by exercise but not by calorie restriction, and how these benefits improve healthspan. Lifespan and healthspan are different things, and improvement in one does not necessarily lead to improvement in the other (as indicated in the figure with a separation line). Most people probably prefer to add life to their years, than merely years to their life.

Interestingly, because calorie restriction and calorie restriction mimetics affect many of the same molecular pathways as exercise, several compounds that are investigated as calorie restriction mimetics can also be classified as exercise mimetics.[112] I will cover both exercise mimetics in-depth in an upcoming article.

Restricting calories vs. carbs

Most of the research on calorie restriction has reduced calories from all macronutrients (protein, fat and carbs). However, the role of each nutritional component in the regulation of lifespan is not well established.[118] Human data shows that a low carbohydrate diet may delay aging in humans by preventing metabolic diseases and improving general health [118], and glucose (the main carbohydrate) has been suggested to speed up aging processed via several mechanisms.[119]

Thus, for humans is seems that restricting carbs is more important than restricting total calories per see. Further support for this comes for research on calorie restriction mimetics. One class of calorie restriction mimetics work by glycolytic inhibition, i.e. by inhibiting glycolysis, which is the biochemical process that breaks down glucose to cellular energy (ATP).[105] Glycolysis can also be reduced by simply eating less carbs, as that causes a metabolic shift that makes the body burn more fat for energy, as opposed to glucose (via glycolysis).

Conclusion

The answers to the scientific debate in response to the question “‘Do you think that calorie restriction can increase longevity in all species, particularly in human beings?’’ neatly summarizes the contrasting views and ambiguity regarding calorie restriction as a strategy for anti-aging in humans [23, 121]:

(1) We do not know for sure.

(2) It is too early to say.

(3) Currently we think so (based on incomplete monkey data).

(4) It cannot work in humans.

(5) We will never know for sure.

The truth is, there is no direct experimental evidence that you will live longer from practicing calorie restriction. Instead of prolongation of life, calorie restriction can more appropriately be regarded as way to prevent premature death caused by obesity.

The key to health and anti-aging in humans is a high energy flux, achieved by regular exercise and nutrient dense unprocessed foods. This will prevent sarcopenia as well as heart disease, which is the number one killer in humans (but not rodents and other species). While some animals can benefit from calorie restriction, we will be better off getting up from our chairs and putting on our sneakers. Keeping a high energy flux via regular exercise and non-exercise activities is an effective strategy for regulating appetite [122-125] and thereby preventing obesity, sarcopenia and cardiovascular disease, which plague humans as we get older (but not rodents, in whom most the benefits of calorie restriction are seen). Ironically, in humans long-term calorie restriction induces hormonal and metabolic effects that actually increase the risk for obesity and its consequences, and thus is a recipe for becoming a miserable couch potato.

In humans, exercise, physical fitness and body composition is more important for health, anti-aging and vital longevity than the caloric intake per see. By implement regular exercise training and non-exercise activities (i.e. reduce your daily sitting time) into your lifestyle, you can physiologically “afford” to eat more while reaping all health benefits and happily enjoying a longer life.

27. de Grey, A.D., The unfortunate influence of the weather on the rate of ageing: why human caloric restriction or its emulation may only extend life expectancy by 2-3 years. Gerontology, 2005. 51(2): p. 73-82.

Exercise measurements were taken before and after 12 week of supplementation and resting metabolic measures were made before and at 6 and 12 week of supplementation. Subjects were instructed to keep their habitual dietary intakes and physical activity levels during the study period.

The 14% increase in resting metabolic rate translated into an increased energy expenditure of 187 calories per day.

In addition, fish oil supplementation reduced triglyceride levels (i.e. blood fats) by 29% and increased lean mass by 4% (3.53 lb or 1.6 kg) and functional capacity by 7% (measured by the “Timed Get Up and Go” [TUG] test). No changes occurred in the placebo group. There was also a small reduction in the inflammatory marker CPR (C-Reactive Protein) when compared to the placebo group.

It was concluded that fish oil supplementation may be a strategy to improve age-related physical and metabolic changes in healthy older females.

Comments

This study confirms findings from some earlier studies that I cited in my previous article “Fish Oil for Muscle Growth and Prevention of Muscle Loss with Aging”, which found increases in lean body mass (muscle mass), energy expenditure and fat burning.

Energy expenditure

While other studies suggested that the increase in resting metabolic rate is primarily due to the increase in lean body (muscle) mass, in this study the increase in energy expenditure at rest and during exercise remained significant even when normalized for body mass and lean mass, suggesting that the increase in lean mass was not the main factor influencing the increase in energy expenditure. A possible contribution to the elevation in energy expenditure could be that fish oil increases the activity of metabolic futile cycles, which are biochemical reaction that expend energy.[2-6] Another explanation – known as the pacemaker theory - suggests that an increase in cell membrane unsaturation results in an elevated metabolic rate by increasing membrane proteins and/or membrane associated processes.[7, 8]

Body fat

Despite the elevation in energy expenditure and fat burning, in this study there was no reduction on body fat.[1] This may be because of the short duration of 12 weeks (3 months) and/or because the subjects consumed a high-carb diet (50% carbs, 20% protein, 30% fat). Previous studies show that high-carb intakes [9, 10], as well as high intakes of omega-6 fats [11], may abrogate the fat loss effect of fish oil.

Lean (muscle) mass gain

The 4% (3.53 lb or 1.6 kg) increase in lean mass in just 3 months is impressive. It should be noted that this study used BIA (bioelectrical impedance) to analyze body composition. Ideally, a more precise measurement of body composition using DEXA (dual x-ray absorptiometry) or MRI (magnetic resonance imaging) should be used in studies investigating effects on interventions on body composition. DEXA and MRI can also show where on the body lean (muscle) is being gained. Nevertheless, a previous study reported a similar increase (3.5%) in thigh muscle lean mass using DEXA [12], indicating that this amount of gain in lean mass may be realistic, at least in this population.

Strength and physical function

Although this study did not find any significant increase in grip strength, a significant 7% increase in physical function, as determined by TUG speed, was demonstrated. It is notable that this was found without any exercise program.[1]

A more recent study in 60 healthy 60-85 year old men and women reported an increase in handgrip strength by 2.3 kg, and an increase in 1-repetition maximum strength by 4% in response to fish oil supplementation (EPA: 1.86 g; DHA: 1.5 g) for 24 weeks.[15] It may be that the 12 week supplementation period in the study reported here was not long enough to evoke increases in strength.

One mechanisms by which fish oil improves physical and muscle function is by increasing the fluidity of the muscle membranes, as well as the sensitivity to acetylcholine [16], which is a neurotransmitter that evokes muscle contractions.

Triglycerides (blood fats) and Inflammation (CRP)

The reduction in triglycerides and CRP seen in this study are not surprising.[1] Fish oil is an effective “drug” for lowering triglycerides (it does so even better than the widely prescribed statin medications) [17, 18], and is well known for its anti-inflammatory effects.[19-22] However, to reduce CRP levels in apparently healthy people a higher dose (at least 3 g EPA + DHA) [1, 23] taken for a longer duration seems to be required, as previous studies providing a low dose fish oil (1.5 to 1.8 g EPA+DHA) [24-26] or being of short duration (less than 8 weeks) [27] did not show any reductions in CRP levels. Also, no reductions in CRP are seen in people with low baseline CRP levels, even at higher doses.[28]

However, the finding that supplementation with extra-virgin olive oil had no effects on inflammatory status (measured by CRP) may come as a surprise, considering that olive oil has well documented health benefits, some of which are related to its anti-inflammatory effects.[29-31] But the lack of effect of extra-virgin olive oil on CRP doesn’t mean it is worthless. For example, polyphenols in extra-virgin olive oil increase the anti-inflammatory effect of HDL (i.e. improves functionality of the “good cholesterol” [32] and decrease atherogenicity of LDL (i.e. make the “bad cholesterol” less bad).[33] Thus using extra-virgin olive oil for cooking is a good idea. Fish oil should not be used for cooking as that will damage (cause lipid peroxidation of) the perishable EPA and DHA fatty acids. If you want the best of both worlds, swallow your fish oil softgels or teaspoons and use extra-virgin olive oil for cooking.

Concluding reflections

Does fish oil increase lean (muscle) mass and strength in young men and women also?

There are currently no studies that have directly compared fish oil effects on body composition parameters in different age groups in the same study under the same conditions (dose, EPA:DHA ratio, duration etc). However, as I outlined in my previous articles, several studies have demonstrated that fish oil supplementation confers benefits for younger adults also in terms of fat loss and anabolic response of muscle protein synthesis to amino acids and insulin. Whether the latter translates into greater muscle mass and strength gains in young folks has not yet been investigated in any study. But considering that the acute response of net muscle protein balance reflects 24-hour balance after exercise and amino acid ingestion [34], and that the enhanced amino acid sensitivity of protein synthesis probably persists for just as long [35], the outlook for fish oil as a muscle anabolic enhancer for any gym rat – regardless of age – is promising.

On January 7th 2016, the new 2015 Dietary Guidelines for Americans were released. One would expect this to be a state-of-the art document with practical hands-on advice that will help people make better food choices and eat healthier. Not so! If you think the new 2015 Dietary Guidelines will tell you everything you need to know about what to eat and what not to eat, you will be greatly disappointed.

I would like to applaud the commentary by Dr. Katz “2015 Dietary Guidelines: A Plate Full of Politics”. Dr. Katz is the director of Yale University’s Prevention Research Center, and president of the American College of Lifestyle Medicine. His summary of the 2015 Dietary Guidelines is “a national embarrassment”.

In this article I will point our some issues that Dr. Katz raised, as well as add my own reflections based on avaliable scientific evidence. To make up for the glaring void of food recommendations, I will end with a practical list of foods you want to eat more of and those to avoid...

Background info

Before looking under the hood of the new 2015 Dietary Guidelines, here’s a summary:

The new Dietary Guidelines were supposed to be based on the Scientific Report of the 2015 Dietary Guidelines Advisory Committee, which was released February 2015. This Scientific Report is intended to inform the federal government of the body of scientific evidence on topics related to diet, nutrition, and health. But as it turns out, the final Dietary Guideline report authors didn't listen to everything....

NOTE: Do not confuse the Dietary Guidelines and its Scientific Report with the specific nutrient intake requirements - such as daily amounts of protein, vitamins and minerals, commonly expressed as the RDA (Recommended Daily Allowance) – which are established by the Food and Nutrition Board of the Institute of Medicine.

The Dietary Guidelines provides food-based guidance for covering requirements. They do so by reviewing American’s nutrient intake and indicators of nutritional status, and potential nutrient-related health outcomes (such as obesity, heart disease and diabetes) to identify “shortfall nutrients” and “overconsumed nutrients”, and then determines whether these nutrients should be designated as “nutrients of public health concern.”

The few good things new 2015 Dietary Guidelines

Before I start trashing the Dietary Guidelines, I want to list 3 good things that they bring to the table:

1. There is no longer any restriction on total fat intake.

2. The previous limit on cholesterol intake has also been removed.

3. A limit on added (aka refined) sugars has been added, urging people to eat less than 10 percent of calories per day from sugar.

However, these points should have been picked up by the guidelines a long time ago. But let’s applaud it is now official - finally!

Problems with the new 2015 Dietary Guidelines

In his commentary, Dr. Katz raises important issues with the new 2015 Dietary Guidelines. The Scientific Report of the 2015 Dietary Guidelines Advisory Committee called for limiting consumption red and processed meat (like bacon), and the International Agency on Cancer Research, a subsidiary of the World Health Organization, has concluded that processed meats are carcinogenic.[1] Despite this, the new 2015 Dietary Guidelines states that “red and processed meats and poultry (in other words, hot dogs and chicken fingers) can be part of a healthy diet as long as the diet doesn’t exceed upper limits for saturated fats and calories.”

Dr. Katz aptly points out that while the 2015 Dietary Guidelines emphasized foods over nutrients, “recommendations about what NOT to eat (or, even, what to limit) are entirely cast in terms of nutrients. We are advised to limit our intake of saturated fat, for instance - but there is virtually no language, and none featured prominently, indicating what foods to avoid to achieve that. Much the same is true of added sugar. Clearly advice about eating less of anything conflicts with the interests of some big industry sector the federal agencies and their bosses in Congress don’t want to upset. So, somehow, we are left to cut back on our intake of saturated fat and sugar while washing down our corned beef with Coca-Cola.”

Nutrient-dense foods… really?

The new 2015 Dietary Guidelines advocate nutrient-dense foods, defined as “Foods that are naturally rich in vitamins, minerals, and other substances that may have positive health effects, and are lean or low in solid fats and without added solid fats, sugars, starches, or sodium and that retain naturally-occurring components such as fiber. All vegetables, fruits, whole grains, fish, eggs, and nuts prepared without added solid fats or sugars are considered nutrient-dense, as are lean or low-fat forms of fluid milk, meat, and poultry prepared without added solid fats or sugars. Nutrient-dense foods provide substantial amounts of vitamins and minerals (micronutrients) and relatively few calories compared to forms of the food that have solid fat and/or added sugars.”

However, in the appendix Table A3-1 “Healthy U.S.-Style Eating Pattern: Recommended Amounts of Food From Each Food Group at 12 Calorie Levels” they allow for half of grain intake to come from refined grain products. For example, for a person who consumes 2,000 calories per day it is ok to eat 3 ounces of ready-to-eat cereal (about 3 cups of flaked cereal) on a daily basis. The photo at the top of the 2015 Dietary Guidelines homepage http://health.gov/dietaryguidelines/2015/guidelines/ even features cereal flakes! Apparently, according to the new 2015 Dietary Guidelines, refined grains are nutrient-dense foods…!

One can question whether humans should eat grains at all.[2-4] Consumption of cereal grains reduces the overall vitamin and mineral content of the diet because cereal grains on average are less nutrient dense for the 13 vitamins and minerals most lacking in the US diet when compared to fish, seafood, lean meat, fresh vegetables and fruits.[2] In addition to being less nutrient dense, the vitamins and minerals that cereal grains provide are of low biological availability.[3] To make it worse, cereal grains contain a variety of anti-nutrients (phytates, alkylresorcinols, protease inhibitors, lectins, etc.) and proteins (gluten) which adversely affect health.[3] Wheat, but also other cereal grains also contribute to the manifestation of chronic inflammation and autoimmune diseases by increasing intestinal permeability and initiating a pro-inflammatory immune responses.[4]

One reason – aside lobbying from the big food industry sector - that cereal grains are heavily recommended by dietary guidelines may be that without them, humanity would likely have never evolved the complex cultural and technological innovations which allowed our departure from the hunter-gatherer niche.[3] However, this does not mean that today’s society will benefit from their continuing consumption. Because of the dissonance between human evolutionary nutritional requirements and the nutrient content of these domesticated grasses, a large number of people suffer diseases and metabolic dysfunction directly attributable to the consumption of cereal grains.[3]

What about salt (sodium) restriction?

Dietary guidelines have urged to us to restrict salt (i.e. sodium) intake for a long time. This is a topic I will cover in more depth in a separate upcoming article. But I want to point out here that the supposed health benefits of salt reduction are heavily debated.[5-11] Americans consume around 3.5 to 5 g sodium per day.[7, 12] The new 2015 Dietary Guidelines urges us to cut sodium intake to less than 2.3 g per day. This despite large studies showing that of over 100,000 subjects showing that sodium intake between 3 and 6 g per day is associated with a lower risk of death and cardiovascular events compared to either a higher or lower level of intake.[13, 14] Thus, guidelines advising restriction of sodium intake below 3 g per day may actually cause is harm.

Saturated fat – should we really limit our intakes?

While the new 2015 Dietary Guidelines have dropped the restriction on cholesterol intake and total fat intake (which they should have done a long time ago), there is still an inordinate focus on limiting saturated fat intake to less than 10%. This despite that the scientific report cited two large meta-analyses showing that saturated fat intake is not associated with an increased risk of heart disease.[15, 16] For ex. a notable meta-analysis including 347,747 subjects followed for up to 23 years showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of coronary heart disease or cardiovascular disease.[16] Another very large meta-analysis of both observational studies and randomized controlled trials concluded that evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.[15] One explanation for previous findings of reduced risk when replacing saturated fat with polyunsaturated fat is that the classification of polyunsaturated fat included both omega-6 and omega-3 fats, and those replaced not just saturated fat but also trans fats (which are well established health enemies [17]).[18, 19]

The most recent meta-analysis (published Aug 2015) concluded that saturated fats are not associated with all-cause mortality, cardiovascular disease, coronary heart disease, ischemic stroke, or type 2 diabetes.[20] This study also urged that dietary guideline authorities carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats, as replacing saturated fat with carbohydrates is associated with development of atherogenic dyslipidemia (i.e. a deleterious profile of cholesterol and fats in the blood)[21] and increased cardiovascular disease risk.[22]

Public health emphasis on reducing saturated fat intake without considering the replacement nutrient or - more importantly - the many other food-based risk factors for cardio-metabolic disease is unlikely to produce the intended benefits.[23, 24] In line with this, the ‘badness” of saturated fat reported in some studies is determined by the specific foods that provide them, and not the amount of saturated fat per se.[24, 25] Specifically, saturated fat from dairy is not harmful and may even reduce risk of cardiovascular disease compared to saturated fat from processed meat.[24, 25]

Critical importance of food processing

Another glaring omission from new 2015 Dietary Guidelines is the total lack of attention given to the health consequences of processed foods. A large body of evidence shows the deleterious effects of food processing on nutrition quality [26-29]; only people who consume the lowest amounts of ultra-processed products (less than approx. 30% of total caloric intake) are anywhere near reaching all nutrient goals for the prevention of obesity and chronic diseases.[30] Mounting data indicates that consumption of ultra-processed may be fueling the epidemics of obesity [31-34] and metabolic syndrome [35], as well as cardiovascular disease.[36]

Considering that ultra-processed foods are dominant is the current food supply [37-40] - in the US they contribute on average almost 1000 calories per day [40] - governments and health authorities should use all possible methods, including legislation and statutory regulation, to halt and reverse the replacement of minimally processed foods by unhealthy ultra-processed food products.[28] Considering this, it is a BIG shame – indeed “a national embarrassment” - that new 2015 Dietary Guidelines are even including refined grain products in their sample menu!

Tell me which foods to eat and which to avoid!

The new 2015 Dietary Guidelines completely failed when it comes to giving people direct and practical recommendations on actual foods to eat and avoid. As of this writing, there is a lot of research showing significant health benefits of dairy, raw (unprocessed) nuts, whole eggs and berries. I will cover each of these in separate upcoming articles. And abandon processed cereals (which currently decorate the homepage of the 2015 Dietary Guidelines!). If you are serious about your health, shun all grain based foods and eat more of fish, poultry, rarely cooked meat, veggies, dairy, raw nuts, whole eggs, berries and fruit. Hopefully the 2025 Dietary Guidelines will included them in their recommendations… in the meantime, make these foods your staple, and your health will be taken care of.

Bottom Line

“Previously, the Dietary Guidelines for Americans recommended that cholesterol intake be limited to no more than 300 mg/day. The 2015 DGAC will not bring forward this recommendation because available

evidence shows no appreciable relationship between consumption of dietary cholesterol and serum

cholesterol, consistent with the conclusions of the AHA/ACC report.”

A recommendation known worldwide that lasted for 47 years has now been discarded and we can all go back to including eggs in our diets. The United States, which was first to promote the “no more than 300 mg cholesterol per day” recommendation, is now one of the last countries to drop it.[41] It is interesting to note that it required a much greater amount of research to prove that egg intake does not increase cardiovascular disease risk than it did to initially condemn it as a significant contributor to cardiovascular disease.

Instead of classifying foods based on botanical or animal origins, a strong case can be made to classify foods based on the extent and purpose of industrial food processing.[42-44] Food processing is defined as “the methods and techniques used by food manufacturers and associated industries to make unprocessed or ’raw‘ foods less perishable, easier to prepare, consume or digest, or more palatable and enjoyable, or else to transform them into food products”.[43] I end this article with a table showing how such a classification can look.

Table: Food classification based on degree and purpose of food processing.[43].

Mounting scientific evidence suggests that current food classification in does not enable solid nutritional

recommendations for prevention of diet-related chronic diseases.[42]

Take home message

Boycott the new 2015 Dietary Guidelines!

Take control of your health by avoiding ultra- processed foods at all cost and by making the following foods a staple in your diet:

26. Luiten, C.M., et al., Ultra-processed foods have the worst nutrient profile, yet they are the most available packaged products in a sample of New Zealand supermarkets. Public Health Nutr, 2015: p. 1-9.

Despite this, two media attention grabbing studies - AIM-HIGH and HPS2-THRIVE - did not find any benefits of niacin supplementation in heart disease patients who were already on intensive statin treatment.

Here I will summarize these studies and expose their multiple flaws, which never made it to the headlines...

AIM-HIGH study

The AIM-HIGH study (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes) was a randomized, multicenter, prospective, controlled clinical trial that was conducted at 92 centers in the United States and Canada, and was published in the New England Journal of Medicine in December 2011.[1]

AIM-HIGH attempted to answer the question whether once LDL cholesterol is reduced with statins, is there an incremental benefit from raising HDL (with niacin)?

A total of 3414 patients, 45 years of age or older, were randomly assigned to receive 1500–2000 mg extended-release niacin or placebo. Both groups received simvastatin adjusted to maintain LDL levels below 80 mg/dL. The primary end-point was the composite of death from coronary heart disease, non-fatal heart attack, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.

The study was terminated early (after 3 years) due to lack of clinically meaningful efficacy; the statin-niacin group and statin-placebo groups had an equal number of deaths/hospitalizations.

However, the AIM-HIGH study had several flaws that precludes drawing any conclusions regarding the efficacy of niacin:

1. The elevation in HDL achieved in the niacin group was only 4 mg/dL higher than that in the placebo group (42 vs. 38 mg/dL).

2. The placebo given to the placebo group was not a “placebo”. Every placebo tablet contained 50 mg immediate-release niacin, and subjects in the placebo group were given 2 to 3 tablets daily, amounting to 100 to 200 mg per day. Importantly, an even lower dose of niacin (50 mg twice daily) was previously reported to increase HDL by 6% in statin treated patients.[2] Thus, AIM-HIGH was actually a comparison between standard-dose (1500-2000 mg/d) and low-dose (100-150 mg/d) niacin, in heavily medicated patients. This likely contributed to the “paradoxical” HDL elevation that was seen in the placebo group.

3. Because niacin also modestly reduces LDL levels, a lipid-lowering algorithm was use to keep the LDL levels between the statin + placebo and statin + niacin groups the same. Therefore, the placebo group received significantly greater doses of simvastatin and ezetimibe than the niacin group, which further complicates interpretation of the results.

4. The early study termination of AIM-HIGH (shortened from planned 4.1 to 3 years) limits study

interpretation because it may have obscured an eventual benefit. In the landmark niacin trial - the Coronary Drug Project – it took 5 years of treatment and 15 years of total follow-up to achieve a significant reduction of heart attacks, strokes and mortality. [3, 4]

5. Nearly 20% of subjects had taken niacin before study entry, and the average dose and duration of that treatment and, more importantly, any effect of pre-study niacin on trial results is unknown. This is important because niacin appears to have a substantial carry-over effect.[4] In the milestone niacin study – the Coronary Drug Project - mortality was not significantly reduced until 5 years of treatment and 10 years of further follow-up after discontinuation of niacin treatment.[4] Thus, pre-study niacin use may have obscured on-study niacin effects, especially given the relatively short study period.

6. A post-hoc sub-analysis of subjects who had both low HDL and high triglycerides found a significant 26-36% reduction in cardiovascular risk.[5] This never made it to the headlines!

HPS2-THRIVE study

The HPS2-THRIVE study (Heart Protection Study 2 - Treatment of HDL to Reduce the Incidence of Vascular Events) included 25,673 subjects, aged 50-80 years, with prior cardiovascular disease, the metabolic syndrome and/or type 2 diabetes, and was published in the New England Journal of Medicine in July 2014.[6]

After 3.9 years, HPS2-THRIVE was stopped due to serious adverse events. The niacin-laropiprant group was more likely to suffer deterioration in diabetes control and had a greater incidence of new onset diabetes, compared to the placebo group. Also, there was a greater frequency of impaired muscle function (myopathy), infection, and bleeding in the niacin-laropiprant group. There was no significant difference in incidence of major cardiovascular events between statin treated patients assigned to niacin-laropiprant vs. those assigned to placebo.

However, like the previous AIM-HIGH study, HPS2-THRIVE unfairly blames niacin for being the bad guy:

1. The study was not designed to investigate the effect of either drug alone. Therefore, niacin cannot be blamed for the negative results.

2. All subjects in the study had excellent lipid levels before the start of the study. This means that HPS2-THRIVE was conducted in patients generally lacking any lipid-related indication for niacin treatment. The National Lipid Association (NLA) published a position paper stating that HPS2-THRIVE “tested a drug in patients who, on average, had no indication to take it.”[7] The NLA also states that niacin is still a valuable statin alternative in statin intolerant patients.

3. Another unfortunate design element was that niacin was always given with laropiprant, a prostaglandin blocker with unknown safety or cardiovascular effects. With regard to safety, the adverse events - impaired muscle function, infection and bleeding - have not been seen in any previous niacin-only studies conducted since the 1950s.[8-10] This suggests that they may have resulted from laropiprant, or from a drug interaction between laropiprant and statin. Indeed, studies show that laropiprant may have effects that counteract the beneficial effects of niacin.[11, 12] Also notable, in the AIM-HIGH – which used the same extended-release niacin but without laropiprant – there was no increase in diabetes incidence.

4. HPS2-THRIVE included subjects of different ethnicities, but reported composite data for all combined. Among the 57% of subjects who were from Europe there was a borderline significant 9% decrease in cardiovascular risk, whereas the 43% of subjects from China had a non-significant (meaning could have been caused by chance) 2% increase. Notably, it was the Chinese population who experienced most of the side effects.

5. Of clinical importance, there was a strong and statistically significant effect of baseline lipids; subjects with LDL levels greater than 58 mg/dL (most of them) at the start of the study had significantly fewer cardiovascular events.

Bottom Line

Thus, to the contrary of widespread media misinformation, neither AIM-HIGH nor HPS2-THRIVE prove that niacin is ineffective or harmful.

Importantly, neither AIM-HIGH nor HPS2-THRIVE apply to people who are NOT taking statins, or those with higher LDL levels at baseline (over 85 mg/dL), high triglyceride levels (over 150-200 mg/dL and low HDL (below 40 mg/dL)

The International Society of Integrative, Functional and Metabolic Cardiovascular Medicine (ISIFMC) refuted the HPS2-Thrive study [12], and The National Lipid Association [13]both concluded that AIM-HIGH and HPS2-THRIVE do not negate the possibility that there may be significant beneficial effects with greater elevation in HDL level.

On the basis of an enormous amount of basic scientific and clinical investigation, the National Lipid Association also highlights the need for continued research on the therapeutic effect of modulating HDL levels, structure and function.[13] As outlined in my previous articles, niacin is a perfect candidate.

What’s important to keep in mind regarding HDL boosting medication studies is that many times the problem is not the target – in this case HDL – but the drug. A prime example is the drug torcetrapib, which despite resulting in an impressive increase of 72% in HDL and a decrease of 25% in LDL caused a 25% increase in heart disease event and a 58% increase in all-cause mortality.[14] This was explained by off-target side effects.[14, 15]

Niacin is – a.k.a vitamin B3 – is an essential vitamin, not a man-made drug that is foreign to the body. The safety and efficacy of niacin has been well-documented, as I’ve outlined in previous articles:

Comments

Therefore, niacin deserves to be defended. It is an innocent natural vitamin which doesn’t possess the big pharma capital and lobbying power. What strikes me is that all modern large statin trials do not include a non-statin comparison group. All they do is add on other drugs and/or niacin (as in the case of the AIM-HIGH and HPS2-THRIVE studies) to a statin-based treatment. Why? Because these studies are extremely resource intensive and very expensive to conduct, that only big pharma has the capital to sponsor. Having a non-statin comparison they would run the risk of it showing to be better than the statin treatment. FDA, the U.S. National Institutes of Health (NIH) and the Institutional Review Boards are definitely are missing in action!

Another reason why most traditional old-school doctors don’t like niacin is because they don’t care to take the time to explain to their patients how to use niacin to beat the flush. I covered this in detail in a previous article:

Thus, there is no problem with niacin. The problems are the flawed studies, misleading media headlines and ignorant doctors! This is why you need to be proactive and take charge of your own health by learning from non-biased medical information resources, and not blindly trust your narrow minded doctor. As medical writer I have the “luxury” to peruse the studies and look at the raw data. I am doing my very best to make it available to the general population – as well as to the minority of good doctors who actually care about providing their patients the best possible care, like Dr. Pierce at Ageless Forever - in a way that can be comprehended and acted upon in real life clinical practice.

In previous articles I have talked about the multiple beneficial effects of niacin supplementation – on both lipids (blood fats and cholesterol) and non-lipid outcomes.

While flushing is often reported to be the main side-effect of niacin supplementation, the flush is a natural reaction to high-dose niacin, and is not dangerous. Thus, while some people may find it uncomfortable, it is not a harmful side-effect. For more on that, see “Niacin - How to Beat the Flush”

Other, potentially harmful side effects, are liver strain/damage, insulin resistance and blood glucose elevations, and uric acid elevations.[1] Here I will summarize what research shows on the severity of these side effects, and whether it is something you should worry about…

Liver strain / damage

Compared to immediate-release niacin, time-release niacin is more liver toxic.[2-8] In doses that achieve equivalent improvements in blood lipid profiles, liver toxicity occurs more frequently with some time-release niacin preparations than with immediate-release niacin.[9] Half of people who take time-release niacin develop some degree of elevations in liver transaminases.[3, 10] In contrast, immediate-release niacin in usual therapeutic doses (up to 3000 to 4000 g per day) almost never causes liver injury.[10, 11] This may seem counterintuitive as immediate-release niacin causes the most intense flush.

One study published 1994 “A Comparison of the Efficacy and Toxic Effects of Sustained- vs Immediate-Release Niacin in Hypercholesterolemic Patients” is commonly cited by critics of niacin supplementation.[8] This study by McKenny et al. concluded that “the sustained-release (i.e. time-release) form of niacin is hepatotoxic and should be restricted from use”.[8] However, it has been criticized because it was clearly designed to maximize the potential for niacin intolerance and toxicity.[12] The study provided subjects with a high dose twice per day (bid) dosing, and intentionally escalated both the immediate-release niacin and time-release niacin to a high total daily dose of 3000 mg (1500 mg twice daily), whether or not subjects had an adequate lipid response at a lower dose.[12] As was pointed out in the critique, if the intent of the study was to show efficacy and minimize intolerance and side effects, a three times per day (tid) or four times per day (qid) dosing scheme would have been used.[12] For example, The Coronary Drug Project (CDP) – which I covered in a previous article “Niacin – a.k.a vitamin B3 – the neglected broad spectrum cholesterol drug!” was such a study, with 1119 subjects on a daily immediate-release niacin dose of 3000 mg, taken is doses of 1000 mg three times per day for up to 6 years. The CDP study had only a 5% dropout rate due to niacin intolerance and toxicity after 1 year of treatment. In contrast, the study by McKenny et al. had a dropout rate of 39% among subjects in the immediate-release niacin group.

The high dose in the study by McKenny et al. is especially troublesome for the time-release niacin group, as it is well known that time-release niacin in high doses may cause liver strain. In their comment on previous studies, McKenny et al. they state "most cases of hepatotoxicity have occurred in patient taking 2000 mg per day or more. Yes, they intentionally administered a dose that exceeds that toxicity threshold by 50%. Two other studies published in the early 1990s independently reported excellent tolerance (dropout rate of only 3-4%) and good lipid (cholesterol and blood fat) responses, using a wax-matrix time-release niacin product (Enduracin).[12, 13] Both of these studies indicated that 1500 mg per day appears to be the average optimal dose of time-release niacin, in this case Enduracin. This data was available at the time the McKenny study was conducted. Despite knowing this they giving subjects twice this dose, 3000 mg per day. It is not surprising that 78% of subjects in the time-release niacin group reported intolerance, with 52% dropping out due to hepatotoxicity.[8]

Another commentary on the McKenny et al. study pointed out that clinical evaluation of relative toxicity requires a comparison of toxic manifestations at doses that provide the same therapeutic benefit, rather than equal doses.[14] Data indicate that the lipid improving potency of the time-release niacin is at least twice that of immediate-release niacin; thus, the side effects of time-release niacin in doses of 1000 to 1500 mg daily should be compared to 2000 to 3000 mg of immediate-release niacin.[14]

The study by McKenny et al. used a time-release niacin product (Goldline Laboratories, Ft Lauderdale, FL) which has been discontinued). Whether their reported dropout rates are due to the high dose or that specific time-release niacin product, or a combination of both, is unknown. However, the study makes the misleading conclusion alluding to that all time-release niacin supplements have harmful effects on the liver, which is wrong. Multiple studies have confirmed the tolerability and liver safety – as well as efficacy in improving cholesterol profiles - of wax-matrix time-release niacin (Enduracin).[12, 13, 15-18]

Before you start niacin supplementation, I recommend that you get your liver enzyme levels checked. Elevated liver enzymes below 3 times the upper limit of normal may initially occur with niacin supplementation but usually resolve with continued supplementation.[19] With elevations greater than that it is advised that the dose is reduced.[20] It is also recommended to take a “liver supplement” like SAMe [21], LIV-52 [22] or milk thistle (a.k.a. silybin) [23], which may protect the liver and help prevent elevations in liver enzymes. SAMe in particular has several human studies supporting its efficacy - at a dose of 800-1200 mg per day - to improve liver function and protect the liver in people who take medications.[21]

Insulin resistance

Niacin supplementation (all forms) may cause a modest, transient, and reversible elevation of fasting blood glucose levels, and in some people also an increase in glycosylated hemoglobin (HbA1c) levels (an indicator of average long-term blood glucose levels).[24] This increase in fasting blood glucose levels and HbA1c is greater in diabetics than non-diabetics.[25, 26]

In the Arterial Disease Multiple Intervention Trial (ADMIT), 468 patients with peripheral arterial disease, including 125 with type 2 diabetes, were randomized to immediate-release niacin (up to 3000 mg/day or maximum tolerated dose) or placebo for 60 weeks.[25] A transient increase of fasting blood glucose levels was found as the niacin dose was up-titrated to 3000 mg, but the elevations returned to baseline levels six weeks after the niacin dosage was stabilized.[25]

In the assessment of diabetes control and evaluation of the efficacy of niaspan trial (ADVENT), 148 patients were randomized to receive extended-release niacin (Niaspan) 1500 mg/day or placebo for 16 weeks.[26] Fasting glucose levels of one third of diabetic patients receiving either 1000 or 1500 mg of Niaspan daily increased between weeks 4 and 8, but returned to baseline by week 16. The 1000 mg/day dose resulted in no significant alteration in glycemic control compared to placebo. The 1500 mg/day dose resulted in modest deterioration of glycemic profile, as indicated by an elevation in HbA1c from 7.21% to7.50%.[26] However, it was stated that any increased risk of microvascular diabetic complications due to this 0.29%-age point increase in HbA1c would likely be offset by the decreased risk of cardiovascular disease thanks to the significant improvements in blood cholesterol and lipoprotein profile.[26] A comprehensive review of the safety aspects of niacin supplementation also concluded that the benefits of niacin far exceed the small deterioration in glucose control.[27]

It was concluded in both ADMIT and ADVENT that lipid-improving dosages of niacin can be safely used in patients with diabetes.[25, 26] In people with diabetes and metabolic syndrome, who are characterized by low HDL levels, the use of a low, more tolerable dose (about 1000 mg/day) can be expected to boost HDL levels by 25%.[11, 28] This is important to underscore as the lipid abnormalities encountered in these patients (low HDL levels and dysfunctional HDL, together with elevated triglycerides and small atherogenic LDL particles) are ideally suited to niacin treatment.

This position is supported by the impressive results from the coronary drug project, where supplementation with immediate-release niacin for 4 years increased fasting blood glucose levels by 7 mg/dL [29] but reduced the risk of 6-year recurrent heart attacks, as well as heart disease death and 15-year total mortality, compared with placebo.[30] These effects were independent of the small elevation in fasting blood glucose.[30] Niacin supplementation in patients with metabolic syndrome conferred the same health benefits (despite a 5.5% increase in fasting blood glucose levels).[31]

Thus, there is good evidence showing that the small increase in fasting blood glucose levels does not negate the overall clinical benefits of niacin supplementation, which is seen even in patients with the metabolic syndrome or diabetes.

Uric acid

Another possible adverse effect of niacin supplementation is a small elevation in blood uric acid levels, which can lead to development of gout.[32] Extended-release niacin in doses up to 2,000 mg/day has been shown to increase uric acid levels by around 11%, but levels still remained within normal limits.[33, 34] In a head-to-head comparison study, the mean increase in uric acid levels was smaller with extended-release niacin than with immediate-release niacin dosed at 500 mg thrice daily (5.8% vs 16.2%, respectively).[35] The increase in uric acid levels after supplementation of 3000 mg/day with immediate-release niacin is of the same magnitude in non-diabetic and diabetic people.[25]

Although the increase in serum uric acid is moderate in patients with normal pre-treatment levels, it can be clinically relevant in patients with high levels of uric acid (over 1.5 times the upper limit of normal) before treatment or in those with pre-existing gout.[36] In these patients, niacin therapy has to be done carefully with low doses (50-100 mg immediate-release niacin per day) and close medical monitoring of uric acid levels.[27] With any increase in serum uric acid of clinical significance, treatment with allopurinol at doses of 100-300 mg per day is recommended.[27] The argument can be made that the tremendous benefits of niacin on blood lipids and cardiovascular disease protection far outweighs the potential risk due to elevation in uric acid in most people.

Summary

As with most things in life, there is a risk-to-benefit ratio. When it comes to niacin, for the large majority of people, the benefits far outweigh any potential side effects.

Despite concerns of liver strain/damage, insulin resistance and uric acid elevations, data shows that therapeutic doses of niacin are safe, even in people with the metabolic syndrome or diabetes.

When considering potential side effects of niacin it should be underscored that according to the US Food and Drug Administration's (FDA) Adverse Event Reporting System, which evaluates the safety of niacin as it is used in daily life, the safety profile of niacin compares favorably with other commonly used cholesterol drugs, including statins and fibrates.[37] The adverse liver effects with prescription extended-release niacin (Niaspan) up to 3000 mg per day are minor, and occur at rates similar to those reported for statin treatment.[38]

If you are looking for an over-the-counter time-release niacin product, get the wax-matrix formulation (Enduracin). The wax-matrix form of time-release niacin has the most research backing up its safety and efficacy in doses around 1500 mg per day. With immediate-release niacin, higher doses of 3000 to 4000 mg per day are safe in most people.

The important thing to remember with niacin is to “start low and go slow” – i.e. to gradually build up the dose - and let your body develop tolerance to the flush. For practical recommendations, see my previous article

- Krill oil supposedly does not cause any fishy burping or other gastro-intestinal side effects.

In this article I will summarize the research on each of these points, and critically evaluate the related marketing claims...

Molecular form of the fat molecule – triglyceride vs. phospholipid

Dietary fat is mainly in the form of triglyceride, the chemical name for fats and oils. These molecules are made up of 4 parts: a glycerol backbone to which three fatty acids are attached.[1] Triglycerides make up 90-95% of the fat we consume in foods.[2]

Another type of dietary fat is phospholipids. These molecules are similar to triglycerides except that the third fatty acid is replaced by a phosphate group that links to a head group (which is typically choline).[1]

In krill oil, some the EPA and DHA is in a phospholipid form and some is in the triglyceride form; in fish oil, they are only in the triglyceride form. It should be noted that commercial krill oil products vary widely, with as little as 19% to 58% of the EPA+DHA being contained in the phospholipid form.[3, 4] In krill oil products currently available on the market, around 30-40% of the EPA+DHA is in the phospholipid form, with the rest in the triglyceride form and a smaller amount in free fatty acid form. Bottom line is that only a portion of the omega-3’s in krill oil are in the phospholipid form. This is important to remember in discussions of krill oil vs. fish oil (see below and an upcoming article on the topic).

It is often claimed that EPA and DHA from krill oil is better absorbed than from fish oil, because phospholipids are supposedly better absorbed than triglycerides. However, there is not much research on this, and data are conflicting. One study found that absorption of EPA and DHA was higher in infants fed a formula containing these fatty acids in the form of phospholipids vs. triglycerides.[5] In contrast, another study that investigated whether phospholipid- or triglyceride-bound DHA was more readily incorporated into red blood cells membranes of term infants showed little difference. What was more important was the fat composition of the overall fat intake rather than the molecular structure (phospholipid vs. triglyceride) in which they are delivered.[6] This was confirmed in another study.[7] Therefore, it appears that absorption of EPA and DHA (at least from infant formulas) depends mainly on the overall fat content and composition of the formula, and that increased intake of EPA and DHA should be encouraged - regardless of their molecular form.[7]

Nevertheless, there are indications that DHA from krill oil, compared from fish oil, may be preferentially incorporated into red blood cell membranes [8] and the brain.[9-13] Regarding neurological and brain-related effects, one study found that supplementation with EPA + DHA in phospholipid form increased visual sustained attention performance in children with inattention compared to the triglyceride form.[14] Another study in healthy elderly found greater improvement in cognitive function after supplementation with krill oil than fish oil.[15]

However, in both these studies low doses of EPA and DHA were used. Bearing in mind that fat composition of the diet and the total amount of EPA and DHA ingested may be more important than the source of EPA and DHA [7], no conclusion about the relative efficacy of EPA and DHA from krill oil vs. fish oil can be made until proper dose-escalation studies are conducted. None have been done so far.

Because the main marketing claim for krill oil states that it is better absorbed and has a greater – some even go as far as saying “superior” - bioavailability that fish oil, I will dedicate a separate upcoming article to this topic.

Astaxanthin

It is true that krill oil contains astaxanthin, which is not found in fish oil. Astaxanthin is a type of a carotenoid found in microalgae and krill [16]. It gives krill oil and salmon (and flamingos!) their pink color. Astaxanthin has several potential health promoting effects.[17, 18] For example, it may be able to slow the progression of neurodegenerative diseases.[19, 20]

However, in order to get any health benefits from astaxanthin, large doses are needed. A study showed that daily doses of 6-12 mg astaxanthin are needed to boost HDL-cholesterol (the ‘good’ particle) levels, while 12-18 mg are needed to increase levels of adiponectin (a health promoting adipokine) and reduce levels of blood fats (triglycerides).[21]

Krill oil provides only 50 to 200 microgram (i.e. 0.05 to 0.2 mg) per 1000 mg (1 gram) capsule. Thus, to get an effective dose of 6 mg astaxanthin you would have to swallow 30 to 120 grams of krill oil. Most krill oil products contain 0.5 or 1 gram per soft gel; thus, this translates to somewhere between 30-240 soft gels per day, which is both practically and financially nearly impossible! If you want effective doses of astaxanthin, it is far more convenient - and a lot cheaper - to just take an astaxanthin supplement.

Choline

Choline was officially recognized as an essential nutrient by the Institute of Medicine (IOM) in 1998.[22] It is a relatively unknown nutrient, which deserves far more attention than it has been getting [23]. (I will cover it more in an upcoming article).

As mentioned in the introduction, the most common “phosphate head group” in phospholipids is choline, and most of the phospholipids in krill oil are phosphatidylcholine (the chemical name of this particular phospholipid molecule). Therefore, krill oil is a source of choline.[24] However, krill oil contains only about 34 g phosphatidylcholine per 100 gram oil, i.e. 340 mg per 1 gram oil.[24] Of this, only 13% is choline itself; thus, krill oil provides about 44 mg choline per 1 gram.

To put this in perspective, the recommended adequate intake (AI) for choline is 550 mg/day.[22] The estimated mean daily intake of choline from food in US adults is 302 mg.[25] Thus, choline is a shortfall nutrient.

While 1000 mg (1 g) of krill oil can help you cover your choline requirement, the cheapest – and by far most nutritious - source of choline is egg yolk. One large egg yolk provides 116 to 190 mg choline.[26] Thus, 1 egg yolk provides 3-4 fold more choline than you get from 1 g of krill oil, without the added cost of krill oil.

Contaminants / Pollutants

It is commonly stated that krill oil is naturally free of toxins and pollutants. The rationale is this: krill is near the bottom of the sea food chain and are caught (mostly) in the relatively clean waters around Antarctica. These two factors should help keep pollutant levels low. It is also sometime claimed that the relatively short lifespan of krill limits the amount of contaminants it can accumulate. However, Antarctic krill live to 5-7 years, which is comparable to - or even longer than - fish species commonly used in fish oil production.[27] In addition, Antarctic krill are highly adaptable feeders; in addition to their herbivorous feeding of phytoplankton (i.e. microalgae) they also eat copepods, zooplankton and detritus (decomposing plant and animal parts, as well as feces).[28] This makes it hard to predict their pollutant levels[28] so directly measuring them is the best way to examine the question.

A comprehensive analytical survey of pollutants in Antarctic krill found that they contain notable levels of hexachlorobenzene (HCB) and p,p'-dichlorodiphenyl dichloroethylene (p,p’-DDE).[29, 30] A follow-up study examined levels of pollutants in commercial krill oil and fish oil products, and compared the pollutant levels in these two classes of supplements.[31]

It was found that none of the categories or products analyzed, even at their highest recommended dose, came close to the tolerable daily intake levels for any single contaminant. However, they all contained several different contaminants. Chlorobenzenes (penta- and hexa-) were found in eight of eleven products at levels ranging from 27–9900 pg at the maximum daily dose of oil. Surprisingly, krill oil products contained higher levels of chlorobenzene than several fish oil products.

Polychlorinated biphenyls (PCBs) were detected in all products. Only the krill oil products contained multiple dioxins and furans. Toxicity equivalencies (TEQ) are available for dioxins, furans and some PCBs. Notably, krill oil featured among the top five highest ranking TEQ products, which also included some low-grade fish oil supplements. High-quality fish oil supplements contained less dioxins, furans and PCBs because these contaminants are efficiently removed by common fish oil cleaning processes (which does not affect the nutritional quality of the fish oil).[32]

Thus, marketing krill oil as being naturally free of toxins and pollutants is clearly not true, however, the levels of these contaminants that one would typically consume by taking krill oil are far below harmful levels. Therefore, the contaminant issue is more about marketing than about a real health concern.

What about the “fishy burping”?

Fish oil is infamous for causing “fishy burps”. Krill oil marketers used this to their advantage, claiming the krill oil does not cause fishy burps. However, a look at the raw data in krill oil studies refutes this, even though most study abstracts state that krill oil is well tolerated.

In one frequently cited study, subjects in both the fish oil and placebo (corn oil) groups had 1 report each of burping of mild and moderate intensity.[33] However, there were 4 and 3 reports of mild and moderate burping in the krill oil group. There were 3 report of mild aftertaste in the fish oil group, but 6 reports of mild aftertaste and 1 report of a stronger aftertaste in the krill oil group. There was 1 report of mild bloating in the fish oil group and 2 reports in the krill oil group. Constipation was only reported in the krill oil group. No statistical analysis was done to compare the frequency of these adverse events between groups, nevertheless the study abstract concludes that “krill oil was well tolerated with no adverse effects”.

Similarly, another study shows increased incidence of gastrointestinal side effects after krill oil compared to fish oil; gas/bloating, 5 vs 0; flatulence, 9 vs 2; diarrhea, 5 vs 2.[34] The increased incidence of gas/bloating and flatulence in the krill oil group over that seen in the fish oil group was statistically significant. In spite of this, it was stated in the study abstract that “No significant differences for other safety variables were noted, including adverse events”.[34]

While burping is clearly not a serious adverse effect, krill oil may have no advantage over fish oil in this regard, and it does not appear to be a substantiated claim.

Cost - price per mg of EPA+DHA

As I will explain further in the upcoming article, regardless what source you use to cover your EPA + DHA needs – krill oil, fish oil or fatty fish - you need to keep an eye on the EPA + DHA content.

In this regard, krill oil has a clear disadvantage. The average cost per 1000 mg krill oil – which typically provides only around 180 mg EPA + DHA – is $1.30

How much EPA + DHA do you need per day?

With all this discussion about EPA + DHA content and bioavailability, you may wonder “ok, but how much EPA + DHA do I need then”? The first thing to know is that “need” is relative depending on what your goals is.

Currently there is no RDI (Recommended daily allowance) for EPA and DHA, but for health promotion and cardiovascular disease prevention, it has been suggested that 1000 mg/day of EPA + DHA is advisable.[35] However, people who have elevated blood fats (triglycerides) need 2000 to 4000 mg per day to achieve a therapeutic benefit.[36] Higher doses of EPA + DHA are also needed if your goal is to improve your body composition; fish oil supplementation can induce fat loss as well as an increase in muscle protein synthesis. I covered these effects in previous articles:

US adults consume on average only 23 mg EPA per day and 63 mg DHA per day from food alone.[37] Thus, supplementation clearly needs to be considered to help people meet recommendations for these long-chain omega-3s.

Summary

Krill oil marketers have seemingly ascribed some magical properties to the phospholipids in krill oil, but these claims don’t hold up under scrutiny.

First, in contrast to what most consumers think, the phospholipid content in krill oil products is typically less than its content of triglycerides (which is what you find in fish oil). So much for the consumer impression that krill oil is all phospholipid.

Second, the amounts of astaxanthin and choline in krill oil are miniscule and not enough to confer any significant health benefits.

Third, krill oil is not “naturally free of toxins and pollutants,” and it can have as much or more than fish oil. But in either case, the levels are vanishing low so neither presents a health hazard.

Finally, if you think krill oil will free you from fishy burps, gas/bloating and flatulence, you may be in for a surprise!

Bottom line, krill oil is a typical example of supplement manufacturers and marketers – and in some cases study authors - selectively and misleadingly reporting study data to their advantage, and making grand extrapolations that have no basis in clinical research.

To cover your needs of EPA and DHA, you can take fish oil or krill oil – but because the latter has less EPA and DHA per gram, you’ll need to take far more capsules to get the same EPA + DHA dose. At a much greater cost!

In an upcoming article I will summarize and comment on the available human studies that have compared krill oil to fish oil. After that discussion you will realize that the supposed “superior” bioavailability of EPA + DHA from krill oil is not that superior. Thus, taking a regular dose of krill oil will only provide you a very minor dose of EPA + DHA, that will not cover your EPA + DHA needs to achieve most health benefits that research has showed with fish and/or fish oil.

32. Maes, J., et al., Removal of dioxins and PCB from fish oil by activated carbon and its influence on the nutritional quality of the oil. Journal of the American Oil Chemists' Society, 2005. 82(8): p. 593-597.

In a previous articles I covered the tremendous health benefits of niacin supplementation, mediated via both lipid (cholesterol and blood fat) and non-lipid mechanisms, and what you need to know about niacin products:

Here I will explain what the notorious niacin flush is all about, and give you hands-on practical tips on how to beat it.

Niacin flush – what’s the fuss about?

Despite niacin’s tremendous health benefits, the infamous flushing has been a major impediment to the clinical use of niacin, and is the main reason for discontinuation of niacin supplementation.[1-3] Most people who start taking a niacin supplement will initially experience the flushing.[1-4] The niacin flush is not dangerous, but can be uncomfortable. The flush manifests as a “prickly heat” or a sense of warmth in the face, neck, ears, trunk, and, less frequently arms and legs.[5] This is often accompanied by itching, tingling and a reddening of the skin, usually in patches (known as erythema).

Symptoms typically start 15-30 minutes after ingesting immediate-release niacin on empty stomach, and 30-120 minutes after ingesting extended-release niacin. Due to inconsistencies in time-release niacin products, their onset of flush occurs at more unpredictable and variable times.[2, 3] The exception is wax-matrix niacin, which is the most reliable time-release formulation.

The flush usually lasts for less than 1 hour to 2.5 hours.[2, 3] For somebody who has never taken a niacin supplement before, as little as 50 mg can result in the characteristic flush.[5] This is why doses should be escalated progressively. Taking an effective dose of 1000 mg (1g) the first time will cause very intense flush reaction over the whole body.[5]

The niacin flush is caused by the release of prostaglandin D2 (and possibly other eicosanoids) from cells in the skin.[6] It was recently demonstrated that niacin also activates the capsaicin receptor - which also mediates the heat sensation caused by consumption of spicy food - and that this activation of the capsaicin receptor contributes to the niacin flush.[7, 8]

Importance of informing people about the flush and how to deal with it

Flushing symptom severity is a strong predictor of niacin discontinuation.[9] One study reported that 27% of niacin users stopped taking niacin after 4 months, and those were the ones who were most bothered by the flush.[9] In contrast, discontinuation rates due to flushing in niacin studies are as low as 5%.[10] A study that specifically evaluate niacin compliance in a “real-world” primary care setting reported discontinuation due to flushing to be 10%.[11]

A shared characteristic among niacin studies reporting low discontinuation rates is the patient education procedures employed prior to study initiation.[10] This suggests that patient education may be a critical factor in niacin supplementation adherence. Support for this comes from a survey of patients in routine clinical practice who were prescribed niacin and reported a high rate of discontinuation; less than half of niacin users reported being advised by their physician to take aspirin to avoid flushing.[9] This underscores the importance of informing people about ways to mitigate the flush.

How to beat the flush?

The onset and intensity of the flush is directly related to the niacin absorption rate and the consequent rate of elevation of blood niacin levels; once a constant blood niacin level is reached the flush starts to abate.[12] Therefore, fast niacin absorption, as seen with immediate-release niacin, causes a greater initial flush intensity than does extended-release niacin, which is absorbed slower.[13-15] However, even extended-release niacin may initially causes a flush reaction. The good news is that there are several ways to reduce the initial intensity of the flush:

Immediate-release niacin should be administered in divided doses, after meals, and doses should be gradually increased.[16] A dose-escalation guideline is to start taking 50-100 mg twice daily for the first

week, then double the daily dose each week until the target dose is reached, ideally 1.5 to 3 g per day.[17] 750 mg taken 2-3 times per day for a total daily dose of 1,500 to 2,250 mg seems to work well for most people.

If you are using time-release niacin – make sure it is was-matrix niacin. I explained why you should chose the was-matrix version of time-release niacin in a previous article “Niacin Supplements - what you need to know about niacin products”. Start taking 250 mg 3 times per day, and build up the dose to 750 mg 2-3 times per day. Always take it after meals.

Extended-release niacin is recommended to be taken at bedtime, after the last daily meal.[18, 19] The prescribing information for extended-release niacin (known as Niaspan) suggests a starting dose of 500 mg for 4 weeks, which is increased in 500-mg increments every 4 weeks to 1 g (two 500-mg tablets) during weeks 5 to 8, 1.5 g (two 750-mg tablets) during weeks 9 to 12, and 2 g (two 1-g tablets) for the final 4 weeks.[20]

Take aspirin 30 min before taking niacin

Several studies shows that aspirin attenuates niacin flushing.[21-27] one study found that 325 mg of aspirin significantly attenuated flushing symptoms when administered 30 to 60 min, but not 15 or 120 min, before ingestion of 500 mg immediate-release niacin.[21] Notably, a higher aspirin dose of 650 mg was not better than 325 mg.[21] However, 325 mg of aspirin is superior to 80 mg in mitigating flushing with 500 mg of immediate-release niacin.[22] 325 mg of aspirin 30 min before niacin ingestion is also significantly superior to 200 mg of ibuprofen in blunting flushing and itching.[23] Taking 325 mg of aspirin 30 min before extended-release niacin (500 to 2000 mg) is also effective, and improves niacin adherence.[25] For greatest reduction in flush intensity, take aspiring before meals and niacin after meals.

Take niacin after meals

Take immediate-release niacin after meals, especially a high-fat meal, as that will slow down its absorption and thus reduce the flush intensity.

Prescription extended-released niacin (Niaspan), which is ingested once daily, should be taken after the last daily meal.

If you take any time-release niacin that is not wax-matrix – such as Slo-Niacin or Niaspan - is it best to take if some 40 min after meals. The reason is that the release mechanism of Slo-Niacin is degraded by peristaltic activity in the gut. Waiting a little bit after a meal will let the gut settle and allow for the time-release complex to work as it is supped to.

Develop tolerance to the flush

Most people don't know that continued niacin supplementation leads to development of tolerance to the flush.[28] This means that the intensity of the flush decreases or even completely vanishes with time, often within the first week or two, as long as niacin is taken regularly on a daily basis.[18, 19, 28, 29] Knowing this is critical, as most discontinuations take place during the first week of niacin supplementation, before tolerance has developed.[29]

Flush tolerance is due in part to smaller increases of prostaglandin D2 production after long-term regular niacin ingestion.[28] However, if niacin supplementation is interrupted, one has to start from scratch and re-develop tolerance, as tolerance only exists as long niacin is taken. Hence, with niacin supplementation one has to stick to it!

Niacin sensitivity

Several studies have shown that many of the people who appear to be intolerant of niacin, primarily because of the flush, are often just more sensitive to niacin and do well on a reduced dose.[30-32] It appears likely that much of what has been presumed to be niacin intolerance may simply be overdosing of niacin in sensitive individuals.[32]

The possibility that some people may have higher niacin sensitivity was demonstrated in an 11 month study with a dose reduction protocol, where niacin sensitive subjects who completed the study on less than 1000 mg/day actually had comparable lipid results to subjects on the full dose of 2000 mg/d.[30] Another study found that taking 435 mg immediate-release niacin per day for 1 year elevates HDL levels by 20% while reducing triglyceride levels by 9%.[33] One study showed that an even lower dose of niacin (50 mg twice daily) increased HDL by 6% in statin treated patients.[34]

Thus, if you cannot tolerate a full dose of immediate-release niacin or time-release niacin, don’t fret. You may still derive substantial health benefits with a lower dose.

BOX: Practical advice on how to take niacin supplements

With immediate-release niacin, start taking 100 mg twice daily for the first week, then double the daily dose each week until the target dose is reached, ideally 1500 to 3000 mg per day.

With time-release niacin – ideally wax-matrix niacin – start taking 250 mg 3 times per day, and build up the dose to 750 mg 2-3 times per day.

Spread out intake over the day and take some 40 min after meals to dampen the niacin flush.

If the flush makes you uncomfortable, taking 325 mg aspirin about 30 minutes prior to niacin reduces the flushing intensity. Try taking the aspiring before meals, and then the niacin after meals.

Stick to it! With regular daily niacin supplementation, tolerance develops to the flush. Over time, the flush sensation can disappear completely in people who diligently keep taking niacin every day.

Summary

Niacin – a.ka. vitamin B3 - is a unique broad spectrum cholesterol “drug”. The reason it has not been getting the attention it deserves in the medical community and among health conscious people, is the flush.

While the niacin flush may be uncomfortable, it is not dangerous; it is a natural reaction to high-dose niacin. As outlined here, there are several simple ways to mitigate this flush. This will help you stick with the niacin supplementation and develop tolerance to the flush, and ultimately reap its wide array of health benefits.